The New 3D Printed Left Atrial Appendage Closure with a Novel Holdfast Device: A Pre-Clinical Feasibility Animal Study.

INTRODUCTION: Many patients undergoing cardiac surgery have risk factors for both atrial fibrillation (AF) and stroke. The left atrial appendage (LAA) is the primary site for thrombi formation. The most severe complication of emboli derived from LAA is stroke, which is associated with a 12-month mortality rate of 38% and a 12-month recurrence rate of 17%. The most common form of treatment for atrial fibrillation and stroke prevention is the pharmacological therapy with anticoagulants. Nonetheless this form of therapy is associated with high risk of major bleeding. Therefore LAA occlusion devices should be tested for their ability to reduce future cerebral ischemic events in patients with high-risk of haemorrhage. AIM: The aim of this study was to evaluate the safety and feasibility of a novel left atrial appendage exclusion device with a minimally invasive introducer in a swine model. MATERIALS AND METHODS: A completely novel LAA device, which is composed of two tubes connected together using a specially created bail, was designed using finite element modelling (FEM) to obtain an optimal support force of 36 N at the closure line. The monolithic form of the occluder was obtained by using additive manufacturing of granular PA2200 powder with the technology of selective laser sintering (SLS). Fifteen swine were included in the feasibility tests, with 10 animals undergoing fourteen days of follow-up and 5 animals undergoing long-term observation of 3 months. For one animal, the follow-up was further prolonged to 6 months. The device was placed via minithoracotomy. After the observation period, all of the animals were euthanized, and their hearts were tested for LAA closure and local inflammatory and tissue response. RESULTS: After the defined observation period, all fifteen hearts were explanted. In all cases the full closure of the LAA was achieved. The macroscopic and microscopic evaluation of the explanted hearts showed that all devices were securely integrated in the surrounding tissues. No pericarditis or macroscopic signs of inflammation at the site of the device were found. All pigs were in good condition with normal weight gain and no other clinical symptoms. CONCLUSION: This novel 3D printed left atrial appendage closure technique with a novel holdfast device was proven to be safe and feasible in all pigs. A benign healing process without inflammation and damage to the surrounding structures or evidence of new thrombi formation was observed. Moreover, the uncomplicated survival and full LAA exclusion in all animals demonstrate the efficacy of this novel and relatively cheap device. Further clinical evaluation and implementation studies should be performed to introduce this new technology into clinical practice.

Solid-phase extraction clean-up of soil and sediment extracts for the determination of various types of pollutants in a single run.

A new sample clean-up procedure based on solid-phase extraction (SPE) sorbents was proposed for the determination of pesticides, polycyclic aromatic hydrocarbons and polychlorinated biphenyls in soils and sediments. The main purpose of the research was to find a combination of sorbents for the SPE method that would permit the determination of many types of analytes (polycyclic aromatic hydrocarbons, polychlorinated biphenyls, N-, P- and Cl-containing pesticides) in a single run. Elution profiles for both the analytes and the interfering components were determined for several types of SPE sorbents (alumina, silica and surface-modified silica) and combinations of them. The efficiency of the clean-up method developed was evaluated using real soil samples.

A diffusion model of a neuron and neural nets.

In the paper a diffusion model of a neuron is treated. A new, less restrictive than usually, condition of applicability of a diffusion model is presented. As a result the point-process-to-point-process model of a neuron is obtained, which produces an output signal of the same kind as the accepted input signals.

Elevated white blood cell synthesis of leukotriene C4 in chronic myelogenous leukaemia but not in polycythaemia vera.

Leukotriene (LT) formation was studied in ionophore A23187-stimulated white blood cell (WBC) preparations from patients with chronic myelogenous leukaemia (CML; n = 14), polycythaemia vera (PV; n = 10) and two control groups consisting of patients with non-malignant inflammatory disease (n = 4) and normal healthy donors (n = 25). The synthesized products were identified and quantitated using high-performance liquid chromatography combined with computerized UV-spectroscopy. White blood cell preparations from the CML patients produced more LTC4 (40.2 +/- 7.9 pmol/10(6) WBC, mean +/- SEM) than WBC from the healthy donors (9.0 +/- 1.8), P less than 0.0005. In contrast, the formation of LTB4 was normal and there was no increase in the total leukotriene synthesis (the sum of LTC4, LTB4, 20-OH-LTB4 and the delta 6-trans-isomers of LTB4). The ratio between leukotrienes C4 and B4 was strongly elevated in the CML group; 1.67 +/- 0.25 v. 0.37 +/- 0.07 in the controls, P less than 0.0005. No significant correlation was observed between the levels of LTC4 and the number of known LTC4 producing cells (such as monocytes, eosinophils and basophils) in the CML WBC preparations. In contrast, a correlation was found between the sum of neutrophilic granulocytes and metamyelocytes in these suspensions and the amount of LTB4 formed; r = 0.600, P less than 0.05. A number of other laboratory or clinical variables of the CML patients (including total white blood cell and platelet counts, differential counts, previous cytotoxic treatment, time from diagnosis, time from last treatment, post study survival and age) did not significantly correlate with the formation of leukotrienes. No abnormality in the production of LTB4 or LTC4 was observed in granulocyte and WBC preparations from the patients with polycythaemia vera and non-malignant inflammatory disease, respectively. The results indicate a selectively increased LTC4 producing capacity in CML.

Delayed-exponential approximation of a linear homogeneous diffusion model of neuron.

The diffusion models of neuronal activity are general yet conceptually simple and flexible enough to be useful in a variety of modeling problems. Unfortunately, even simple diffusion models lead to tedious numerical calculations. Consequently, the existing neural net models use characteristics of a single neuron taken from the "pre-diffusion" era of neural modeling. Simplistic elements of neural nets forbid to incorporate a single learning neuron structure into the net model. The above drawback cannot be overcome without the use of the adequate structure of the single neuron as an element of a net. A linear (not necessarily homogeneous) diffusion model of a single neuron is a good candidate for such a structure, it must, however, be simplified. In the paper the structure of the diffusion model of neuron is discussed and a linear homogeneous model with reflection is analyzed. For this model an approximation is presented, which is based on the approximation of the first passage time distribution of the Ornstein-Uhlenbeck process by the delayed (shifted) exponential distribution. The resulting model has a simple structure and has a prospective application in neural modeling and in analysis of neural nets.

Prostacyclin in patients with peptic gastric ulcers--a placebo controlled study.

A double-blind study on prostacyclin (5 ng/kg/min infused i.v. for 5 hrs per day during 6 consecutive days) for the treatment of peptic gastric ulcers was carried out in thirty patients (15 prostacyclin, 15 placebo). Gastroscopy and its scoring was performed 1-2 days before the treatment, as well as a day and a week after the course of treatment was completed. Basal acid output (BAO) and pentagastrin stimulated release of gastric acid (maximum acid output MAO; peak acid output PAO) were measured before the treatment, during the third infusion, and one day after all the infusions had been completed. At the same time the basal release of bicarbonate into gastric juice was determined. Prostacyclin significantly accelerated healing of the ulcers at the end point of the study. Simultaneously, in the prostacyclin-treated patients an increase in bicarbonate release into gastric juice was noted, although the acidity of gastric juice was not changed. Our study shows a cytoprotective action of prostacyclin on a damaged human gastric mucosa.

Release of disaggregatory prostanoids into circulation by nicotinic alcohol, nicotinic acid and nicotinamide.

Nicotinic alcohol, nicotinic acid and nicotinamide caused disaggregation of platelet clumps formed on collagen strip superfused with blood of anaesthetized cats. This effect was completely blocked by pretreatment of cats with 50 mg/kg of acetyl salicylic acid. Disaggregatory substance formed in cat's blood disappeared when blood had been passed through silicone coil warmed to 37 degrees C for 15 min. None of the tested substances had any disaggregatory activity when applied directly on collagen strip. It is postulated that the effect of nicotinic acid derivatives is mediated by prostacyclin which they release.

Antiaggregatory effects of flavonoids in vivo and their influence on lipoxygenase and cyclooxygenase in vitro.

Quercetin, rutin and troxerutin were found to inhibit platelet aggregation on collagen strip superfused with blood of anesthetized cats. Quercetin was the most potent acting at the dose of 1 micrograms/kg. Its effect was shortlasting. Troxerutin was a weak inhibitor of platelet aggregation and its effect was delayed. Quercetin inhibited in 50% 15-lipoxygenase and 12-lipoxygenase in vitro at the concentration of 1.3 microm and 13 microM respectively. It stimulated cyclooxygenase when 100 microM of arachidonic acid was applied. Quercetin inhibited cyclooxygenase in the presence of 1.6 microM of substrate. Rutin was a weaker inhibitor of lipoxygenase. Troxerutin was inactive in all experiments in vitro. It is concluded that unusually strong effect of quercetin in vivo can be explained neither by its influence on cyclooxygenase nor on lipoxygenase because the effects in vitro were observed in much higher concentrations.